Trifluoromethyl sulfone



United States Patent 1 Claim. (Cl. 260--607) This application is adivision of our copending application Serial No. 788,499 filed January23, 1959, now US. Patent No. 3,061,645.

This invention relates to p-=(trifluoromethylthio)-benzaldehyde and toits preparation.

This compound can be represented by the formula:

and can be prepared from previously known materials by novel methodswhich we have discovered. These methods involve the preparation of anumber of new intermediate organic compounds.

In accordance with this invention, using as a starting materialp-(methylthio)benzaldehyde, a known compound described in US. Patent2,761,873, some of our methods for the production of the compound ofFormula 1 can be diagrammatically represented as follows:

at e4 Various alternative procedures will be apparent from an inspectionof the above diagram. Thus, one route of synthesis involves steps (a)and (e); a difierent route involves steps (a), (c), (f) and (g); a thirdroute involves (b), (d), (f) and (g); a fourth route involves steps (b),(d), '(h) and (i). The choice of one of these routes will depend on anumber of factors, such as the amount of material to be produced, theequipment avail- 3,207,792 Patented Sept. 21, 1965 able, the economicsof the particular situation, etc. preferred route is CHr-SQCHO lHgSOs.

With reference to the above diagram, it Will be seen that the knownp(methylthio)benzaldehyde is converted to the novelalpha,alpha-dichloro-p-tolyl trichloromethyl sulfide by either of twomethods. Thionyl chloride can be used instead of phosphoruspentachloride, if desired.

The alpha,alpha-dichlo1'o-p-tolyl trichloromethyl sulfide is reactedwith three equivalents or slightly more of hydrogen fluoride, in apressure vessel, at an elevated temperature of about 100 C., andpreferably between and 200 C., to form the novel trifluoromethylthioderivative, which is then readily converted to the desired aldehyde ofFormula 1 by reaction with sulfuric acid, preferably at a temperaturewithin the range from about 20 to 50 C.

The conversion of alpha,alpha-dichloro-p-tolyl trichloromethyl sulfideto the trifluoromethyl compound is The carried out by heating atatmospheric pressure with antimony trifluoride, with an antimonypentahalide, with antimony trifluoride mixed with an antimonypentahalide, or with antimony trifluoride mixed with hydrogen fluoride.

Alternatively, as can be seen by step (e) in the above diagram, thenovel p-(trichloromethylthio)benzaldehyde is converted directly to thecompound of Formula 1 by reaction with HF or SbF or similar fluorinatingreagent.

Steps (a) and (d) shown above can be carried out with or without asolvent. Solvents such as methylene chloride, chloroform, carbontetrachloride, tetrachloroethane, benzene, pentane, hexane,chlorobenzene or toluene, to name a few, may be used. The reaction canbe carried out between 30 C. and C., but it is best carried out between0 C. and 50 C.

Steps (b) and (c) shown above can likewise be carried out with orwithout a solvent. Any solvent unreactive with phosphorus pentachloridemay be employed. Carbon tetrachloride, methylene chloride, benzene,hexane, pentane or chloroform are suitable. The reaction is exothermic,and can be carried out from 20 C. to 200 C., but is conveniently carriedout at 0 C. to 50 C.

Step is carried out by heating the alpha,alpha-dichloro-p-tolyltrichloromethyl sulfide in three moles ofliquid hydrogen fluoride in abomb between 50 to 130 C. for /2 to 3 hours. The reaction will go atatmospheric pressure by cooling hydrogen fluoride to the compound over along period of time (48 to 100 hours). In the process at atmosphericpressure one chlorine is exchanged at a time and it is possible toisolate the intermediate compounds:

r o12os-o r101, more-s-Q-orron Step (f) may alternatively be carried outby heating alpha,alpha-dichloro-p-tolyl trichloromethyl sulfide atatmospheric pressure with a mole of antimony trifluoride. A pentavalentantimony salt may if desired be used as a catalyst. This reaction can becarried out without a solvent, but an inert solvent such aschlorobenzene, nitrobenzene, toluene, xylene or tetrachloroethane may beused. The temperature of the reaction is from 50 C. to 200 C.

Step (h) is carried out as outlined above for (f) with antimonytrifluoride but in this case, 1% moles to 2 moles of SbF is used foreach mole of alpha,alpha-dichloro-p-tolyl trichloromethyl sulfide.

Step (e) is carried out as indicated for step (f) but starting withp-(trichloromethylthio)benzaldehyde.

Step (g) is readily carried out by stirring alpha,alphadichloro-p-tolyltrifluoromethyl sulfide with 1 to 6 parts of concentrated sulfuric acidat ambient temperature. The range of temperature is from to 100 C.

Step (i) is like step (g) except that the alpha,alpha-difluoro-p-tolyltrifluoromethyl sulfide is reacted with the sulfuric acid at highertemperature (50 to 100 C.).

'In a new and related process, the novel alpha,alpha-dichloro-p-tolyltrifluoromethyl sulfide is reacted with an oxidizing agent, such asperacetic acid, chromic acid, acidic potassium permanganate, or thelike, to form another useful compound identified as-alpha,alpha-dichlorop-tolyl trifluorornethyl sulfone. This process isillustrated by the equation:

The compounds of the present invention are useful in the preparation ofother organic compounds. Some of them are also useful in the control ofthe growth of microorganisms and are fungicidal and nematocidal agents.The compound of Formula 1 is particularly useful as a substitutedbenzaldehyde in the processes shown in US. Patent 2,816,915 for thepreparation of certain phenylam-idopropanediols known to have usefulbactericidal properties and to be especially useful in the control ofrickettsial infections. The novel alpha,alpha-dichloro-ptolyltrifluoromethyl sulfone is a particularly useful intermediate which canbe readily reacted With sulfuric acid at elevated temperatures on theorder of 50 to 100 C. to provide good yields of the known compoundp-(trifiuorornethylsulfonyl)benzaldehyde, disclosed as a useful materialin the aforementioned US. Patent 2,816,915. This process is illustratedas follows:

The invention will be further illustrated but is not intended to belimited by the following examples illustrating the novel compounds andmethods of preparation:

. EXAMPLE 1 Alpha,alpha-dichloro-p-tolyl trichloromethyl sulfide Asuspension of 1647 g. (7.9 moles) of phosphorus pentachloride in 1500cc, of carbon tetrachloride is stirred in a 5 1. RB. flask equipped witha dropping funnel, thermometer and a condenser and drying tube. Theaddition of 1072 g. (7.04 moles) of p-(methylthio)benzaldehyde isstarted at a temperature of 24 C. The temperature rises to 30 C. andcooling is applied to keep the temperature between 2530 C. The additionrequires about 32 minutes. The PCl goes into solution during this time,except for a few small lumps. The mixture is stirred an additional 30minutes and the solution is complete. A 5 ml. sample is removed andconcentrated under reduced pressure. The crystalline residue isrecrystallized from pentane to give 0.3 g. of pale yellow crystalsmelting 4647 C. This is alpha-alpha-dichloro-p-tolyl methyl sulfide.

A gas inlet tube dipping beneath the surface is placed in the flask andchlorine bubbled into the solution. Cooling is applied to keep thetemperature 2025 C. A voluminous evolution of hydrogen chloride takesplace. A total of 1726 g. (20.31 moles) of chlorine is added over 4hrs., 26 minutes. There is free chlorine in the solution. The solutionis then sparged with nitrogen and warmed with a Water bath until theexcess chlorine is removed, and the remaining solution is thenconcentrated on a Water pump. A considerable amount of PCl sublimes tothe upper part of the apparatus. The residue is poured into 4 l. of iceand water and 1.5 1. of methylene chloride added to dissolve the productwhich crystallizes. The methylene chloride layer is separated, and theWater extracted with 500 cc. of methylene chloride. The combinedextracts are dried over magnesium sulfate and concentrated, leaving 2214g. of yellow oil which solidifies.

A 5 g. sample is recrystallized from pentane to give 2.4 g., M.P. 56.557C.

EXAMPLE 2 Alpha,alpha-dichloro-p-tolyl trifluoromenhyl sulfide A oneliter Hastelloy B bomb is charged with 627 g. ofalpha,alpha-dichloro-p-tolyl trichloromethyl sulfide, and after pumpingthe air from the bomb it is charged with 135 g. of hydrogen fluoride.The bomb is heated to C. for 1 hour, cooled in a Dry Ice bath, and thehydrogen chloride slowly bled from the bomb. After the pressure isreleased, the contents of the bomb are transferred to a polyethylenebottle, and the bomb washed out with methylene chloride and thiscombined with the contents of the bottle. This is stirred with aTefloncoated stirring bar on a magnetic stirrer and powdered calciumcarbonate added slowly to prevent excessive foaming. When all of the HFand HCl have been neutralized, the liquid is filtered.

The combined filtrates from three runs are flash dis tilled at 0.2 mm.pressure through a short Vigreux column. A yield of 733 g. of product isobtained, B.P. 63 67 C., n =1.5158.

EXAMPLE 3 Alpha,alpl1a-dicl1l0r0-p-tolyl trifluoromethyl sulfide A 310g. (0.783 moles) portion of alpha,alpha-dichlorop-tolyl trichloromethylsulfide is melted and added to 200 g. of antimony trifluoride in a 2 1.RB. flask equipped with thermometer, stirrer and condenser. The mixtureis heated to 122 C. and the temperature held between 125 for 1% hrs.This is then poured into 2 l. of 6 N HCl containing some ice. Theproduct is extracted with methylene chloride, dried over magnesiumsulfate and concentrated at 10 mm. pressure. The product is dis tilledat 8 mm. pressure through a short Vigreux column. The yield is 101 g. ofcolorless oil n =1.5187. This product contains two main constituents,With a third. lesser component. The main fraction is the desired Thenext fraction is mc-s-Q-oum This mixture is hydrolyzed by stirring with200 cc. of conc. sulfuric acid at 25-30 C. for 1 hr. The solution ispoured upon 2 1. of ice and water, and the solid extracted withmethylene chloride, to give 83 g. of residue, which is distilled at 8mm. pressure through an 18" spinning band column to give 58 g. ofp-(trifluoromethylthio) benzaldehyde. This product :on vaporchromatographic analysis proves to be better than 95% pure.

EXAMPLE 4 Alphraalpha-diohlora-p-tolyl trifluoromethylsulfone A solutionof 175 g. (0.673 mole) of alpha,alpha-dichloro-p-tolyl trifluoromethylsulfide in 175 cc. of glacial acetic acid is stirred in a R.B. flaskequipped with a thermometer, dropping funnel and condenser. The flask isheated on a steam bath to 80 C. and 265 g. of 40% peracetic acid isadded slowly. The heat is removed and the temperature maintained at80-90 by controlling rate of addition of the peracetic acid. The firsthalf of the oxidation is quite exothermic, but heated may be necessaryfor the second half of the oxidation.

After all of the peracetic acid is added, the temperature is held at 90C. for 1% hours. The total reaction time is three hours. The mixture iscooled to room temperature, poured into 1 1. of ice and Water andextracted with methylene chloride. The methylene chloride extract isback washed with sat. sodium bicarbonate until neutral, dried overmagnesium sulfate, and concentrated. The product is distilled at 9 mm.and the fraction boiling 139- 148 amounts to 173 g., n =l.5093.

EXAMPLE 5 p-(Trifluoromethylthio)benzaldehyde A mixture of 50 g. (0.192mole) of alpha,alpha-dichloro-p-tolyl trifluoromethyl sulfide and 100cc. of cone. sulfuric acid is stirred at room temperature in a K13.flask equipped with a thermometer and condenser. The temperature dropsand a vigorous evolution of hydrogen chloride takes place. The solutionturns orange-red. After 2 hrs., the acid is poured into 1 l. of ice andwater and a white solid separates. This is extracted with methylenechloride, dried over magnesium sulfate and concentrated under reducedpres-sure. The product is distilled through a Vigreux column at 8-10 mm.pressure, and boiled at 83 to 85. The yield is 33.4 g. of a white solid,M.P. 27-28 C.

EXAMPLE 6 p-(Trifluoromethylsulfonyl) benzaldehyde A mixture of 168 g.(0.575 mole) of alpha,alpha-dichloro-p-tolyl trifluoromethylsulfone and340 cc. of conc. sulfuric acid is stirred in a RB. flask equipped with athermometer and condenser. The flask is heated on a steam bath to 86 C.,when HCl is evolved. The temperature is raised to C. for 1% hours. Thesolution is then poured upon 2 l. of ice and Water. The productseparates as oil, which soon crystallizes. The solid is filtered, washedwith water, then dissolved in methylene chloride, dried over magnesiumsulfate, and concentrated. The product is distilled through a shortVigreux column at 9 mm. The fraction boiling at 124-131 C. amounts tog., M.P. 39.5 to 41 C.

EXAMPLE 7 p(Trichloromethylthio) benzaldehyde A solution of 100 g.(0.657 mole) of p-(methylthio) benzaldehyde in 500 cc. of carbontetrachloride is stirred at 24-30 C. as 140 g. (1.97 mole) of chlorineis added over a three hour period. The solution is then sparged withnitrogen to remove the hydrogen chloride, and the carbon tetrachlorideis removed by distillation under reduced pressure leaving 166 g. This ispoured into 300 cc. of hexane and the product crystallized. This isfiltered, washed with hexane and dried. There is obtained 103 g. ofproduct, melting 73-75 C.

EXAMPLE 8 Alpha,alpha-dichl0r0-p-t0lyl trichloromethyl sulfide A mixtureof 103 g. (0.403 mole) of p-(trichloromethylthio)benzaldehyde and 84 g.(0.403 mole) of phos phorous pentachloride is prepared which rapidlyturns liquid with evolution of heat. The reaction is controlled bycooling the mixture. After the reaction is complete, the phosphorusoxychloride is distilled off under reduced pressure. The oil thatremains is poured into 1 l. of ice and water. The crystalline product isfiltered, washed with Water and dried. The yield is g., M.P. 52-54 C.The pnoduct can be purified by crystallization from pentane.

The invention claimed is:

A compound of the formula FaC-SOz-Q-CHCM References Cited by theExaminer UNITED STATES PATENTS 2,180,772 11/39 Scherer 260599 2,870,2151/59 Davis et a1. 260-607 2,993,075 7/61 Heininger et al. 260-5993,045,050 7/62 SChoot et a1. 260607 3,047,631 7/62 Rocklin 260-607 OTHERREFERENCES University of North Carolina, Organic Fluorine Compounds(received by Library October 2, 1950), page 277.

Wagner-Zook: Synthetic Organic Chemistry, 1953, page 801.

CHARLES B. PARKER, Primary Examiner.

LEON ZITVER, Examiner.

